Positive Correlation Between Clearance of High-Risk Human Papillomavirus and Lack of Residual Disease After Loop Excision of the Transformation Zone in Early Stage Cervical Cancer.

OBJECTIVES: In cervical cancer, a number of pathological parameters have been explored for their utility in tailoring a less aggressive approach for patients with low-risk early stage disease. We examined whether, in patients with cervical cancer stage IA1 to IB1, diagnosed by loop excision of the transformation zone (LLETZ), positive for high-risk human papillomavirus (hrHPV), clearance of hrHPV after LLETZ correlates with absence of residual disease at the final pathology after definitive or further surgery. MATERIALS AND METHODS: Data were collected from patients diagnosed with early stage invasive cervical cancer and positive hrHPV DNA, who had a repeat cervical HPV test 3 to 12 weeks after LLETZ and before final surgical treatment. We compared characteristics of patients with post-LLETZ negative and positive hrHPV. RESULTS: Of 28 patients, 13 were post-LLETZ negative hrHPV; of these, 11 did not have residual cancer in the final pathological specimen; two patients had cervical intraepithelial neoplasia 3. Of the 15 women who had post-LLETZ positive hrHPV, 10 had residual cancer in the final pathological specimen and 3 had cervical intraepithelial neoplasia or adenocarcinoma in situ; only 2 were negative for cancer. The post-LLETZ hrHPV test shows a sensitivity of 86.7% and specificity of 84.6%. CONCLUSIONS: Clearance of hrHPV from the cervix after LLETZ was found to correlate with the absence of residual cancer in the final surgical specimen. Testing for hrHPV post-LLETZ might serve as a new parameter for risk assessment and tailoring of a less radical operation in women with early stage cervical cancer.

Palliative care in ovarian carcinoma patients-a personalized approach of a team work: a review.

Most ovarian cancer patients are diagnosed in an advanced stage; and after the initial treatment experience disease recurrence, which eventually becomes palliative. Many questions arise in this setting including how to address patients in the palliative setting, how to discuss end-of-life issues, and how to manage symptoms. In this review, we discuss the timing and setting of end-of-life discussion in the context of end-stage ovarian cancer. We review the approach to relieving disease burden by improving and decreasing symptoms. These symptoms include recurrent ascites, bowel obstruction, pain, pulmonary effusion, and deep vein thrombosis.

[LOW GRADE OVARIAN CANCER].

INTRODUCTION: According to the new and reproducible grading system of the MD Anderson Cancer Center (MDACC), low grade serous cancer (LGSC) differs greatly from the commonly known high grade serous cancer (HGSC). Pathology speaking, LGSC has less mitotic index; the grade of nuclear atypia is low to intermediate. Genetically speaking, these tumors tend to show mutation in the mitogen-activated protein kinase (MAPK) pathway, mainly in the KRAS and BRAF genes, resulting in uncontrolled proliferation; however, it seems that the presence of this mutation might be related to a better prognosis compared to their absence. The presenting symptoms and spread is similar to HGSC, such as the elevated Ca-125 and the advanced stage at the presentation. The rate of proliferation, on one hand affects the prognosis and therefore, although it tends to present in advanced stages such as HGSC, the prognosis is better. On the other hand, low proliferation might be the reason for the relative decrease in the sensitivity to the common chemotherapy given in HGSC. Treatment strategy, as well. is similar to HGSC consisting of debulking surgery followed by or after chemotherapy. Molecular and pathology studies confirm borderline tumor might be a precursor of some of LGSC, since it shares similar mutation pathways seen in LGSC. Those pathways are targets for newer chemotherapy agents, currently under phase II and III promising trials.

High Incidence of Carcinosarcoma among Patients Previously Treated with Tamoxifen.

BACKGROUND: Tamoxifen acts as an estrogen antagonist within the breast tissue. In the uterus, tamoxifen is an agonist for some estrogen receptors and therefore can cause hyperplasia or neoplasia in the endometrium. OBJECTIVES: To compare characteristics of patients with uterine sarcoma who were and were not previously treated with tamoxifen. METHODS: The medical records of all women with uterine sarcoma who had been treated at the Carmel Medical Center in Haifa, Israel, during 2000-2013 were retrospectively reviewed. Disease characteristics, histological type of sarcoma, patient demographics, treatments and final outcomes were compared between patients who had and those who had not been exposed to tamoxifen. RESULTS: Of the 66 patients identified, 14 (21%) had been exposed to tamoxifen, one of them for 3 years and 13 for at least 5 years. Mean ages were 69 ± 8 and 66 ± 12 years for those exposed and those not exposed to the drug, respectively. Rates of uterine carcinosarcoma were 86% (12/14) and 44% (23/52), respectively (P < 0.006). Patients with carcinosarcoma were older than other sarcoma patients (73 ± 7 vs. 59 ± 11 P < 0.005).There were no statistically significant differences between the two groups in rates of diabetes mellitus, hypertension, dyslipidemia or heart disease. The mean time from diagnosis to death was 7.37 ± 0.42 years. The overall survival rates of carcinosarcoma patients were not statistically different from that of other sarcoma patients. Tamoxifen exposure was not associated with overall survival among all sarcoma patients, nor among the subgroup of carcinosarcoma patients. CONCLUSIONS: Tamoxifen treatment was associated with elevated incidence of carcinosarcoma among women with uterine sarcoma, but was not found to be associated with prognosis or with co-morbidities.

Characterization of the median sacral artery course at the sacral promontory using contrast-enhanced computed tomography.

INTRODUCTION AND HYPOTHESIS: Laparoscopic sacral colpopexy (SC) is increasingly utilized in the surgical management of apical prolapse. It involves attachment of a synthetic mesh to the sacral promontory and to the prolapsed vaginal walls. The median sacral artery (MSA) runs close to the site of mesh attachment and is therefore prone to intraoperative injury, which may lead to profound hemorrhaging. The aim of this study was to determine the location of the MSA at the level of the sacral promontory with regard to adjacent visible anatomical landmarks. Surgeons may use this information to reduce the risk for presacral bleeding. METHODS: Sixty consecutive contrast-enhanced pelvic computed tomography scans were revised, and the location of the MSA at the level of the sacral promontory was determined in relation to the ureters, iliac arteries, sacral midline, and aortic bifurcation. RESULTS: The MSA runs 0.2 ± 3.9 mm left to the midline of the sacral promontory and 48.0 ± 15.4 mm caudal to the aortic bifurcation. The ureters, internal and external iliac arteries on the right were significantly closer to the MSA than on the left (30.0 ± 7.1 vs 35.2 ± 8.8 mm, p = 0.001; 21.5 ± 6.8 vs 30.3 ± 8.4 mm, p < 0.0001; 32.8 ± 10.2 vs 41.9 ± 14.5 mm, p = 0.005 respectively). CONCLUSIONS: The MSA, which runs left to the midline of the sacral promontory, and its location can be determined intraoperatively in relation to adjacent visible anatomical structures. The iliac vessels and ureter on the right are significantly closer to the MSA than those on the left. This information may help surgeons performing SC to avoid MSA injury, thus reducing operative morbidity.

The prevalence of HPV types in women with CIN 2-3 or cervical cancer in Haifa district, Israel.

BACKGROUND: Human papilloma virus (HPV) is classified as a biologic carcinogen causing cervical cancer. Our aim was to identify all the HPV types responsible for cervical cancer and pre-cervical cancer in Israel. METHODS: This study included 226 women, diagnosed with cervical intraepithelial neoplasia (CIN) 2-3 and 115 women diagnosed with cervical cancer, and tested for all HPV typing during the period of January 2006 to May 2013. RESULTS: HPV was detected in 92.9% of women with CIN 2-3 and high-risk HPV (HR-HPV) was detected in 85.8% of them. In women with cervical cancer, HPV was positive in 96.5%, HR-HPV detected in 93%. In the CIN 2-3 group the most common HPV types were 16 (42%), 31 (8.8%) and 18 (4.9%) and in the cancer group HPV 16 (57.4%), 45 (9.6%), and 18 (7.8%). Multiple HPV types were seen in 12.8% of CIN 2-3 group but only in 0.9% of cancer group. The chief complaint led to cancer diagnosis was post menopause bleeding (27%), while abnormal Papanicolaou (Pap) test lead to CIN 2-3 diagnosis in 75.2% of the women. Only 22.6% of women diagnosed with cancer were diagnosed due to abnormal Pap test and 76.9% of them were diagnosed at stage I, as compared to women diagnosed with cancer because of bleeding or abnormal mass, of them 57.1 % were diagnosed at stage I (P<0.07). CONCLUSIONS: HR-HPV types were found in 93% of cancer group and 85.8% of CIN 2-3 group, and low-risk HPV (LR-HPV) was detected in 3.5% and 7.1% of women with cervical cancer and CIN 2-3 respectively. The most common HPV types in cervical cancer women were 16, 45 and 18. Women diagnosed with cancer because abnormal Pap test were in earlier stage compared to women diagnosed because of complains. Including LR-HPV types in screening HPV can increase the sensitivity of the test.

Vaginal cuff closure technique and the risk for infected pelvic hematoma after vaginal hysterectomy.

OBJECTIVES: Infected pelvic hematoma is a relatively common complication of vaginal hysterectomy, manifesting with postoperative pain and fever which often necessitate surgical drainage. We aimed to assess the effect of the surgical technique for vaginal cuff closure on the incidence of this complication. STUDY DESIGN: Until March 31, 2010, our surgical protocol for vaginal hysterectomy included complete vaginal cuff closure. After this date, all surgeries were performed using another technique, by which a patent tract was left at the vaginal cuff for drainage of blood, secretions and debris. We reviewed medical records of all women who underwent vaginal hysterectomy for pelvic organ prolapse in our institution between January 2006 and November 2015, including demographic, clinical and surgical data. We compared the incidence of postoperative infected pelvic hematomas before and after March 31, 2010. RESULTS: We identified 325 women who underwent vaginal hysterectomy during the first time period (group I) and 243 women who underwent this procedure during the second time period (group II). While demographic and clinical data were not significantly different between the two groups, the incidence of infected pelvic hematomas necessitating hospitalization was significantly lower in group II (3.8% vs. 13.5%, p<0.0001). CONCLUSIONS: A significant reduction in the incidence of infected pelvic hematoma following vaginal hysterectomy was noted using a surgical technique that allows for drainage of blood and debris through the vaginal cuff.

Low-grade serous ovarian cancer: A review.

Epithelial ovarian cancers can be divided into the more common, aggressive type II cancers and the less common, slow-growing type I cancers. Under this model, serous ovarian carcinomas can be subdivided into high-grade (type II) and low-grade (type I) tumours. The two-tier system for grading serous ovarian carcinomas is superior to more detailed grading systems in terms of predicting survival. Low-grade serous carcinomas typically present in young women and have a relatively good prognosis, despite being resistant to chemotherapy. Low-grade serous cancers have a high prevalence of KRAS and BRAF mutations, but a low prevalence of TP53 mutations (which are characteristic of high-grade serous cancers). Among women with low-grade serous ovarian cancer, the presence of a KRAS/BRAF mutation is a favorable prognostic factor. Studies of the mitogen-activated protein kinase (MAPK) inhibitor in low-grade serous ovarian cancer suggest that identifying MAPK mutations might eventually be useful in guiding treatment.

Vulvar and Vaginal Cancer, Vulvar Intraepithelial Neoplasia 3 and Vaginal Intraepithelial Neoplasia 3: Experience of a Referral Institute.

BACKGROUND: Vulvar and vaginal malignant and premalignant lesions are uncommon and are clinically heterogeneous diseases with two pathways of carcinogenesis: human papillomavirus (HPV) induced or non-HPV induced. OBJECTIVES: To evaluate the demographic and clinical characteristics associated with vulvar or vaginal cancer and vulvar and vaginal intraepithelial neoplasia 3 (VIN3, VAIN3). METHODS: We conducted a retrospective chart review of 148 women with vulvar and vaginal malignancy and pre-malignancy for the period October 2004 to October 2012, and identified 59 and 19 patients with vulvar and vaginal cancer respectively, and 57 and 13 patients with VIN3 and VAIN3 respectively RESULTS: The median age of vulvar cancer patients was 30 years older than that of VIN3 patients. HPV was found in 60% and 66.6% of vulvar and vaginal cancer patients respectively, and in 82.3% and 84.6% of patients with VIN3 and VAIN3 respectively. A history of cervical intraepithelial neoplasia (CIN) or warts was observed in 10% and 10.5% of vulvar and vaginal cancer patients respectively, and in 57.9% and 46% of patients with VIN3 and VAIN3 respectively. In 52.6% of patients the vaginal cancer was metastases from other organs. CONCLUSIONS: Most women with vulvar carcinoma are older than 70 years. VIN3 and VAIN3 are associated with HPV infection and the most prevalent type is HPV16. Almost half the vaginal cancers are associated with metastases from other organs and almost half of VAIN3 is associated with past cervical dysplasia or carcinoma.

Transvaginal repair of a urethrovaginal fistula using the Latzko technique with a bulbocavernosus (Martius) flap.

INTRODUCTION AND HYPOTHESIS: Urethrovaginal fistula is a rare disorder that may occur following sling procedures for stress urinary incontinence, excision of a urethral diverticulum, anterior vaginal wall repair, radiation therapy, and prolonged indwelling urethral catheter. The most common clinical manifestation is continuous urinary leakage through the vagina, aggravated by an increase in the intra-abdominal pressure. Appropriate management, including timing of the surgical intervention and the preferred technique, remains controversial. METHODS: This video presentation describes the transvaginal repair of a urethrovaginal fistula using the Latzko technique and a bulbocavernosus (Martius) flap. RESULTS: The patient's postoperative course was uneventful. At her follow-up visit 2 months later, she was free of urinary leakage, and a pelvic examination revealed excellent healing, with complete closure of the fistula. CONCLUSIONS: Transvaginal repair using the Latzko technique with a vascular bulbocavernosus (Martius) flap is an effective and safe mode of treatment.

Two-Dimensional Sonographic Evaluation of Endometrial Polyps - Parameters That Are Reassuring.

AIMS: To assess intra-endometrial lesions according to five two-dimensional sonographic parameters for predicting malignancy. MATERIAL AND METHODS: This is a retrospective analysis of stored digital images from consecutive pathological reports of patients with benign endometrial polyps and stage 1 endometrial carcinoma. Five sonographic parameters were evaluated: heterogeneous or complex echogenicity of the lesion, presence of a 'bright edge sign,' regular endometrial-myometrial junction, the presence of a normal endometrium adjacent to the lesion, and detection of small intralesional cysts. The sensitivity, specificity, PPV, and NPV of these parameters were calculated, as well as combinations of pairs of parameters. RESULTS: Seventy-nine patients were eligible for the current study, 26 with benign endometrial polyps and 53 with stage 1 endometrial carcinoma. The sonographic appearance of numerous small intralesional cysts (cystic formation) was highly related to benign polyp; the presence of a lesion with heterogeneous echogenicity had sensitivity and specificity for malignancy of 63.5 and 88.5%, respectively. CONCLUSIONS: We have shown that asymptomatic endometrial lesions, which are homogenous, have bright edges, and small intralesional cysts are likely to be benign Determining these parameters during sonographic evaluation can assist in identifying patients who will benefit from a follow-up strategy instead of an unnecessary surgical intervention.

Surgical removal of a large vaginal calculus formed after a tension-free vaginal tape procedure.

Vaginal calculus is a rare disorder which has been reported in association with urethral diverticulum, urogenital sinus anomaly, bladder exstrophy and the tension-free vaginal tape (TVT) procedure. We report a 42-year-old woman who presented with persistent, intractable urinary tract infection (UTI) following a TVT procedure. Cystoscopy demonstrated an eroded tape with the formation of a bladder calculus, and the patient underwent laser cystolithotripsy and cystoscopic resection of the tape. Following this procedure, her UTI completely resolved and she remained asymptomatic for several years. Seven years later she presented with a solid vaginal mass. Pelvic examination followed by transvaginal ultrasonography and magnetic resonance imaging demonstrated a large vaginal calculus located at the lower third of the anterior vaginal wall adjacent to the bladder neck. This video presents the transvaginal excision and removal of the vaginal calculus.

The mutual effect of pregestational body mass index, maternal hyperglycemia and gestational weight gain on adverse pregnancy outcomes.

OBJECTIVE: To investigate the mutual effect of obesity, gestational diabetes (GDM) and gestational weight gain (GWG) on adverse pregnancy outcomes. METHODS: Charts of patients who delivered in our hospital between June 2001 and June 2006 singleton, live births >24 weeks gestation were reviewed. Univariate and multivariate logistic regression were used to assess pregnancy outcomes defined as large for gestational age (LGA), primary cesarean section (PCS) and a composite outcome of LGA and/or PCS. RESULTS: A total of 8595 women were included. Frequency of composite outcome increased with increasing body mass index (BMI), increasing hyperglycemia and above-recommended GWG. In the multivariate logistic regression analysis compared to women with normal BMI, odds ratio (OR) for composite outcome was 1.23 (95% confidence interval [CI] 1.06-1.44) in overweight women, OR = 1.86 (1.51-2.31) in obese women and in severe obesity OR = 2.97 (2.15-4.11). Compared to normoglycemic women, odds for composite outcome in women with abnormal glucose challenge test OR = 1.46 (1.20-1.79), impaired glucose tolerance OR = 1.65 (1.14-2.4) and GDM OR = 1.56 (1.16-2.10). Women with GWG above recommended had OR = 1.58, (1.37-1.81) for composite outcome. CONCLUSIONS: Higher pregestational BMI, maternal hyperglycemia and above-recommended GWG independently contribute to adverse pregnancy outcomes. Furthermore, there is mutual effect between these three factors and adverse outcomes. Appropriate pregestational weight and adequate GWG might reduce risk of adverse pregnancy outcomes.

The prognostic significance of hematological parameters in women with uterine serous papillary carcinoma (USPC).

OBJECTIVES: Preoperative hematologic parameters: thrombocytosis, leukocytosis and anemia have been demonstrated to be independent poor prognostic factors in ovarian and endometrial cancers. However, little is known about their relation to uterine serous papillary carcinoma (USPC). We evaluated several preoperative hematologic parameters and their association with clinicopathologic features, disease progression and overall survival in USPC patients. STUDY DESIGN: This was a retrospective cohort study reviewing charts of all patients with a histologic pure USPC at two gynecologic oncology centers from January 2000 through July 2012. All patients had comprehensive hematologic tests prior to primary surgical treatment and were exposed to the same adjuvant treatment protocol. RESULTS: The study included 56 patients, mean age at diagnosis 69.4±15. Six (11%) had platelet count above 400000 10(6)/L, of them four (66%) were dead at the end of follow up (HR=1.4, p=0.48; CI 95% 0.5-4.3). The mean hemoglobin level was 12.3g/dl, fibrinogen 437.5mg/dL and lymphocytes 2013/µL. None of these parameters was significantly associated with 5 year survival. Leukocyte and neutrophil levels were adversely associated with survival. Of 15 patients with leukocytosis >10000/µL, 67% were dead at the end of follow up (HR=3.98, p=0.003; CI 95% 1.6-9.8). Of the 27 with neutrophils above 65%, 14 (52%) were dead at the end of follow up (HR=3.1; p=0.015; CI 95% 1.2-7.8). CONCLUSIONS: In patients with USPC, leukocytosis and neutrophilia are associated with aggressive tumor biology, and may predict a lower 5 year survival.

Clinical and Pathological Characteristics of Incidental Diagnostic Early Occult Malignancy After Risk-Reducing Salpingo-Oophorectomy in BRCA Mutation Carriers.

OBJECTIVE: Carriers of familial BRCA mutations are at high risk of early development of ovarian tubal or peritoneal cancers. The definite preventative treatment for these cases is early, risk-reducing, bilateral salpingo-oophorectomy (BSO). The aims of the study were to describe the incidence and source of early occult malignancy after risk-reducing salpingo-oophorectomy in carriers of Ashkenazi Jewish BRCA mutations and to characterize the clinical and pathological features of this unique population. METHODS: Data were collected retrospectively regarding women who underwent BSO in our gynecologic oncology unit from January 2002 through July 2012, after a positive test for a BRCA1 or BRCA2 mutation. RESULTS: The following 92 cases of BRCA mutations were included: 53 BRCA1, 37 BRCA2, and 2 with both mutations. After risk-reducing salpingo-oophorectomy, 5 (5.4%) of the patients were found to have early occult adnexal malignancy upon pathology study. All 5 had the BRCA1 185 del-AG mutation. Three of the 5 malignancies originated from the ovaries and 2 in the fallopian tubes with no involvement of the ovaries. CONCLUSIONS: A 5.4% incidence of early occult malignancy in adnexal pathology of BSO was found in carriers of Ashkenazi Jewish BRCA mutations. Two cases with malignant origins within the fallopian tube, while sparing the ovaries in their entirety, support the fallopian tubes as the originating organ for some ovarian or peritoneal malignancies in BRCA mutation carriers.

p27 and its ubiquitin ligase Skp2 expression in endometrium of IVF patients with repeated hormonal stimulation.

This preliminary study examined a possible effect of long duration repeated hormonal stimulation on the endometrium using a molecular tool. The expression of the hormone stimulated, cell cycle regulators, p27 and its ligase S-phase kinase-interacting protein2 (Skp2), were assessed in 46 endometrial samples of patients who underwent repeated IVF cycles (3-21). Skp2 protein is usually undetectable in normal tissue and can be demonstrated only in rapidly dividing cells. Samples from non-stimulated, normal cycling women served as control group A. Samples of endometrial carcinoma served as control group B. In secretory endometrium, the expression of p27 was found to be lower and Skp2 higher in the study group compared with control group A. Moreover, in 25% of patients of the study group, Skp2 expression was significantly higher (P < 0.05) compared with control group A, reaching concentrations demonstrated in endometrial carcinoma. The findings of this study suggest that repeated hormone stimulation cycles may disrupt endometrial physiology, potentially towards abnormal proliferation. These changes in protein expression are described for the first time in IVF patients and should be further investigated.

Vaginal adhesions after transvaginal pelvic reconstructive surgeries: prevalence and clinical implications.

INTRODUCTION AND HYPOTHESIS: Our aim was to assess the prevalence of vaginal adhesions after transvaginal pelvic reconstructive surgeries and evaluate relevant risk factors and impact on surgical outcome and sexual function. METHODS: This was a retrospective study examining medical records of all patients undergoing transvaginal pelvic reconstructive surgeries for pelvic organ prolapse (POP) at our institution between January 2006 and December 2007. RESULTS: One hundred and ninety -nine women were included in the study, of whom 165 had a comprehensive pre- and postoperative follow-up assessment and were available for final analysis. Vaginal adhesions were reported in 18 (10.9%) women during the first follow-up visit 36 ± 34 days postoperatively. Adhesions were reported to be successfully separated manually in all cases during pelvic examination. Patients with or without vaginal adhesions showed no statistically significant differences in demographic, obstetric, or clinical characteristics or in severity of prolapse. No statistically significant correlation was found between any specific surgical procedure and the risk of developing vaginal adhesions. Rates of prolapse recurrence, postoperative vaginal narrowing and dyspareunia were not significantly different between groups. CONCLUSIONS: Vaginal adhesion formation is a relatively common complication after transvaginal pelvic reconstructive surgeries unrelated to preoperative degree of prolapse or to the type of surgery. If adhesions are separated manually at an early stage, surgical outcome and sexual function do not seem to be adversely affected.

[INTRAVENOUS CHEMOTHERAPY VERSUS INTRAPERITONEAL CHEMOTHERAPY IN ADVANCED OVARIAN CANCER: UPDATE ON THE SITUATION WORLDWIDE AND IN ISRAEL].

Ovarian cancer is the second in incidence and the first cause of death. As much as 70% of ovarian cancer patients are diagnosed with advanced disease. The standard treatment of advanced ovarian cancer is a combination of primary optimal debulking (POD) followed by a combined adjuvant chemotherapy treatment. Another optional treatment includes neoadjuvant chemotherapy followed by optimal debulking and then adjuvant chemotherapy. The common adjuvant chemotherapy includes a combination of platinum and taxol compounds given intravenously. Other possible treatments which had been evaluated in the past decades include a combination of chemotherapy given intravenously and intraperitoneally. The rationale behind delivering the chemotherapy intraperitoneally is to provide a much higher concentrations of cytotoxic agents in the peritoneal cavity and to reduce the systemic side effects. A number of randomized trials have shown that the combination of IV and IP chemotherapy entails a survival advantage. Most studies included treatment based on cisplatin treatments with/ without taxol given intravenously versus a combined treatment (intravenously and intraperitoneally) of those agents. An advantage of up to 8 months in disease-free survival and 11 months in overall survival was noted in the IP group. On the other hand, this treatment led to a higher rate of side effects, including abdominal pain, electrolyte imbalance and catheter related complications. Despite the inconsistency in the treatment protocols between the different trials comparing intravenous and intra-peritoneal treatment, one cannot ignore the statistical significance between the groups, for disease-free survival and overall survival. That is why, when addressing patients who completed optimal surgery, one needs to conduct a thorough evaluation regarding the complementary chemotherapy treatment. Due to the broad side effect profile, special notice should be taken as to the patient's age, medical history, and performance status after the primary surgery and her ability to endure an aggressive chemotherapy treatment. By doing so, it will be possible to select the ovarian cancer patients who will benefit he most from combining intravenous and intraperitoneal treatment.

[CHALLENGING THE OPTIMAL NUMBER OF RETRIEVED OOCYTES AND ITS IMPACT ON PREGNANCY AND LIVE BIRTH RATES IN IVF/ICSI CYCLES].

INTRODUCTION: Large numbers of retrieved oocytes are associated with higher chances of having cryopreservation of embryos. However, the process entailed exposes women to increased risk for ovarian hyperstimulation syndrome. Furthermore, mild ovary stimulation protocols are more patient-friendly and with less adverse effects. Only limited reports exist on the significance of the number of retrieved oocytes achieved in a single stimulation cycle. AIM: To investigate the optimal number of retrieved oocytes to achieve pregnancy and live birth. METHODS: This retrospective analysis included 1590 IVF cycles. Oocytes maturation, fertilization, cleavage, as well as pregnancy and live birth rates were analyzed according to the number of retrieved oocytes. RESULTS: Oocyte maturation, fertilization and cleavage rates were lower in cycles with more than 10 retrieved oocytes compared with other groups. Live birth rates were highest when the number of retrieved oocytes was 11-15. CONCLUSIONS: Retrieval of more than 15 oocytes was not associated with a significant increase in chances of conception and birth. DISCUSSION: The better oocyte quality with 10 or less oocytes retrieved could be the result of a possible interference with the natural selection, or the minimized exposure of growing follicles to the potentially negative effects of ovarian stimulation. Although the average number of available embryos was higher when more than 10 oocytes were retrieved, achievement of more than 15 oocytes did not improve IVF outcome in terms of pregnancy and delivery rates. SUMMARY: Analysis of 1590 IVF cycles including the frozen-thawed transfers shows that the best outcomes were achieved with an optimal number of 11-15 oocytes.

[PRENATAL GENETIC DIAGNOSIS-- "DAYS OF FUTURE PAST"].

This review describes the history and the evolvement of prenatal genetic screening tests. We start in the era prior to the understanding that certain syndromes are genetic, continue through the identification of their genetic basis and the changes in markers in the pregnant woman's serum and conclude in the present when assays such as cell free D.N.A are offered to high risk women.